Efficacy and Safety of GLPG1205 in Subjects With Active Ulcerative Colitis (ORIGIN)

Phase II, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of GLPG1205 in Patients With Moderate to Severe Ulcerative Colitis

• Approximately 60 patients suffering from moderate to severe ulcerative colitis will be evaluated for improvement of disease activity (efficacy) when taking GLPG1205 or matching placebo once daily for 12 weeks in addition to their stable background treatment.
• During the course of the study, patients will also be examined for any side effects that may occur (safety and tolerability), and the amount of GLPG1205 present in the blood (Pharmacokinetics) as well as the effects of GLPG1205 on disease- and mechanism of action-related parameters (Pharmacodynamics) in blood, stool and colonic biopsies will be determined.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: GLPG1205; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • St. Pierre University Hospital Center
  • Leuven, Belgium
    • Leuven University Hospital
  • Liege, Belgium
    • Clinic Saint-Joseph
• Czech Republic
  • Hradec Kralove, Czech Republic
    • Hepato-Gastroenterology HK Ltd.
  • Pilsen, Czech Republic
    • Outpatient Clinic of Internal Medicine and Gastroenterology
  • Usti nad Orlici, Czech Republic
    • Orlickoustecka Hospital, Inc.
  • Zlin, Czech Republic
    • Regional Hospital T. Bata, Clinic of Internal Medicine
  • Znojmo, Czech Republic
    • Hospital Znojmo
• Germany
  • Berlin, Germany
    • Gastroenterology Specialist Practice
  • Hamburg, Germany
    • Asklepios West Hospital Hamburg, Clinic of Internal Medicine
  • Hannover, Germany
    • Hannover Medical School
  • Jena, Germany
    • University Hospital Jena
  • Minden, Germany
    • Gastroenterology Group Practice Minden
  • Muenster, Germany
    • Gastroenterology Practice at Germania-Campus
  • Oldenburg, Germany
    • Internal Medicine Group Practice Oldenburg
• Hungary
  • Budapest, Hungary
    • ClinExpert Medical Center
  • Budapest, Hungary
    • Hungarian Center for Obesity Ltd.
  • Budapest, Hungary
    • Medical Centre, Hungarian Defence Forces
  • Budapest, Hungary
    • Szent Margit Hospital
  • Debrecen, Hungary
    • Main Railway Outpatient Clinic Debrecen
  • Vac, Hungary
    • Javorszky Odon Hospital
• Poland
  • Ksawerow, Poland
    • Healthcare Center Orkan Med Stec Michalska Spolka Jawna
  • Lodz, Poland
    • Saint Family Hospital Medical Center
  • Sopot, Poland
    • Sopmed Llc
  • Tychy, Poland
    • H-T Medical Center
  • Warsaw, Poland
    • Maternal, Pediatric and Adolescent Healtcare Centre, Gastroenterology Diagnostic Facility for Adults
  • Warsaw, Poland
    • Vivamed
  • Wroclaw, Poland
    • Active Health Center, Non-Public Healthcare Facility Zawidawie Center
• Russian Federation
  • Kazan, Russian Federation
    • Kazan State Medical University
  • Krasnoyarsk, Russian Federation
    • Territorial Clinical Hospital
  • Moscow, Russian Federation
    • Central Research Institute of Gastroenterology
  • Moscow, Russian Federation
    • Moscow Vladimirsky Regional Clinical Research Institute
  • Nizhny Novgorod, Russian Federation
    • Semashko Nizhny Novgorod Regional Clinical Hospital
  • Novosibirsk, Russian Federation
    • City Clinical Hospital #12
  • Penza, Russian Federation
    • Penza Regional Clinical Hospital n.a. N. N. Burdenko
  • Saint Petersburg, Russian Federation
    • City Clinical Hospital #31
  • Saint Petersburg, Russian Federation
    • City General Hospital #2
  • Saint Petersburg, Russian Federation
    • St. Venerable Martyress Elizabeth Municipal Hospital
  • Stavropol, Russian Federation
    • Stavropol State Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects between 18 and 75 years
• Documented history of UC
• Presence of active UC for a minimum period of 14 days prior to screening and spread beyond the rectum, Mayo score ≥ 6 with rectal bleeding score ≥ 1 and endoscopy score ≥ 2
• Absence of infectious colitis
• Tumor necrosis factor alpha (TNFα) inhibitor-naive subjects should have failed at least 1 prior conventional therapy
• Continuation of concurrent treatment with oral steroids (≤30 mg prednisolone eq/day), immunosuppressants and 5-aminosalicylates at stable dose is allowed
• Female subjects must have a negative blood pregnancy test, unless they are surgically sterile, had a hysterectomy, or have been postmenopausal for at least 1 year
• Subjects will have to use highly effective contraceptive methods

Exclusion Criteria:

• History of sensitivity to any component of the study drug, or a history of drug or other allergy
• Any concurrent illness, condition, disability, or clinically significant abnormality that, in the investigator's opinion, represents a safety risk for the subject's participation, may affect the interpretation of data, or may prevent the subject from safely completing the assessments
• History of significant psychological, neurologic, hepatic, renal, endocrine, cardiovascular, GI (other than UC), pulmonary, or metabolic disease
• History of active infections requiring intravenous antibiotics within the past 4 weeks prior to screening.
• History of malignancy within the past 5 years; presence or history of intestinal malignancy
• History of bowel surgery within 6 months prior to screening; history of colon resection with < 30 cm of the colon remaining
• Suspicion of Crohn's disease, indeterminate colitis, microscopic colitis, ischemic colitis, diverticular disease-associated colitis, or radiation-induced colitis
• Subject who has received non-permitted UC therapies within specified timeframes, depending on the medication, as stated in the protocol
• Subject who is pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLPG1205 100mg QD; GLPG1205 100mg daily dosing in the morning	Drug: GLPG1205; GLPG1205 daily dosing in the morning for 12 weeks
Placebo Comparator: Placebo; Placebo daily dosing in the morning	Drug: Placebo; placebo daily dosing in the morning daily for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Mayo score at Week 8	To evaluate the efficacy of GLPG1205 in terms of changes in Mayo score comparing results at Week 8 with baseline between GLPG1205 treated subjects and placebo subjects	Screening and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in partial Mayo score	To evaluate the efficacy of GLPG1205 in terms of changes in partial Mayo score comparing results with baseline between GLPG1205 treated subjects and placebo subjects at every visit up to Week 12	From Screening to Week 12
Histological response rate	To evaluate the efficacy of GLPG1205 in terms of histological response rate by use of the histopathological Geboes index comparing results at Week 8 with baseline between GLPG1205 treated subjects and placebo subjects	Screening and Week 8
Number of subjects with adverse events	To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of adverse events at every visit	From Screening to Week 16
Number of subjects with abnormal laboratory parameters	To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal laboratory parameters at every visit	From Screening to Week 16
Number of subjects with abnormal vital signs	To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal vital signs at every visit	From Screening to Week 16
Number of subjects with abnormal electrocardiogram	To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal electrocardiograms at every visit	From Screening to Week 16
Number of subjects with abnormal physical examination	To evaluate the safety and tolerability of GLPG1205 between GLPG1205 treated subjects and placebo subjects in terms of abnormal physical examination at every visit	From Screening to Week 16
The plasma levels of GLPG1205	To characterize the pharmacokinetics (PK) of GLPG1205 by measuring the amount in plasma at Week 4, 8 and 12	Week 4, 8 and 12
Changes in serum C-reactive protein (CRP) levels	To characterize the pharmacodynamics (PD) of GLPG1205 by measuring the levels of C-reactive protein in serum at every visit	From Screening to Week 16
Changes in faecal calprotectin levels	To characterize the pharmacodynamics (PD) of GLPG1205 by measuring the levels of faecal calprotectin in stool at every visit up to Week 12	From Screening to Week 12
Changes in myeloperoxidase (MPO) levels in colonic biopsies	To characterize the pharmacodynamics (PD) of GLPG1205 by measuring the levels of myeloperoxidase (MPO) in colonic biopsies at Screening and Week 8	Screening and Week 8

Collaborators and Investigators

• Sponsor: Galapagos NV

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 9, 2015
• First Submitted That Met QC Criteria: January 9, 2015
• First Posted (Estimate): January 13, 2015

Study Record Updates

• Last Update Posted (Estimate): November 20, 2015
• Last Update Submitted That Met QC Criteria: November 18, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: moderate to severe ulcerative colitis; GLPG1205
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative
• Other Study ID Numbers: GLPG1205-CL-211; 2014-001893-32 (EudraCT Number)